A-DREAM (Alliance A032101): Intermittent ADT+ARPI interruption delivers 41% 18‑mo treatment-free eugonadal recovery in mHSPC

A-DREAM is a single-arm Phase 2 de-escalation strategy testing interruption of testosterone suppression (ADT/TS) plus an androgen receptor pathway inhibitor (ARPI) after an “exceptional response” (PSA<0.2ng/mL on therapy with castrate testosterone) in metastatic hormone-sensitive prostate cancer; eligible patients had already received TS for 540–750 days and ARPI for ≥360 days before stopping both (n=78). At 18 months after treatment interruption, 58% (45/78) remained treatment-free and 67% (52/78) recovered testosterone; the primary endpoint—treatment-free at 18 months with testosterone recovery—was 41% (32/78; 80% CI 33.5–48.9; one-sided p=0.0249), with 35% restarting protocol TS+ARPI by a median follow-up of 21.2 months. There’s no direct SOC comparator because current mHSPC SOC is continuous ADT intensification with an ARPI (±docetaxel), but historically intermittent vs continuous ADT in metastatic HSPC (pre-ARPI era) raised concerns about outcomes in some subgroups (e.g., SWOG S9346 suggested worse OS with intermittent therapy in “minimal disease,” HR 1.23), so this modern ARPI-era “stop after deep response” approach will likely need longer-term PFS/OS plus QoL and subgroup (volume/risk) readouts before it can be viewed as broadly practice-changing.